Merck & Co., Inc. announced Friday that it has discontinued the evaluation of
twice- daily dosing regimens of its HIV protease inhibitor, Crixivan(R)
(indinavir sulfate), in combination with reverse transcriptase
inhibitors (RTIs).

Merck recommends that patients in the twice-daily dosing arms in these
studies be changed to a regimen with the approved dosing (800 mg every
eight hours) of Crixivan to ensure that they receive optimal therapy.
Merck will continue to study twice-daily dosing of Crixivan in
combination trials with other protease inhibitors.

The Company had initiated two studies to compare the antiviral efficacy
and tolerability of the approved 800 mg three-times daily dosing with
twice- daily dosing (1,200 mg every 12 hours) of Crixivan. The first
study compared Crixivan twice-daily versus Crixivan three-times daily,
each in combination with the RTIs AZT(a) and 3TC(b), in patients
starting antiretroviral therapy. The second, a transition study,
evaluated the two dosing regimens (Crixivan twice-daily with RTIs and
three-times daily with RTIs) among patients who had already achieved
levels of virus below detection after six months on therapy with the
approved three-times daily dosing of Crixivan with RTIs.

The decision is based on data from an interim analysis of the initial
therapy study at week 24 that showed that the three-times daily regimen
was more effective than the twice-daily regimen in reducing levels of
viral RNA to below detection (less than 400 copies/mL) in patients
initiating therapy. At week 24, 91 percent of patients on the approved
dosing regimen had achieved viral levels below 400 copies/mL, compared
to 64 percent of patients on the twice-daily regimen.
"Although the initial therapy study provided us with additional evidence
of the potent antiviral effect of Crixivan dosed every eight hours in
combination with AZT and 3TC," explained Bach-Yen Nguyen, M.D.,
director, Clinical Research, Merck Research Laboratories, "the
difference in efficacy between the two treatment arms over time
indicates that the approved dosing regimen and the twice-daily dosing
regimen are unlikely to reach equivalence."

Crixivan in combination with other antiretroviral agents is indicated
for the treatment of HIV infection. Crixivan can help reduce the chance
of illnesses and death associated with HIV as demonstrated in clinical
trials of approximately one year. Patients currently on treatment with
Crixivan should continue to take their medication as prescribed by their
physicians. Physicians treating patients with Crixivan should consult
the prescribing information.

Other Studies with Twice-Daily Crixivan Continue

Other studies now under way by Merck to evaluate the antiviral activity
of twice-daily dosing of Crixivan combined with other protease
inhibitors dosed twice-daily, such as nelfinavir and ritonavir, are
continuing.

Potent Antiviral Effect Seen with Approved Dosing of Crixivan

The Merck studies were part of the Company's commitment to evaluate
further the twice-daily dosing regimen in larger numbers of patients in
an attempt to confirm encouraging antiviral results seen in a
twice-daily dosing pilot study. Like the earlier pilot study, the
larger twice-daily initial therapy study evaluated patients who had not
received prior treatment with a protease inhibitor or 3TC. This study
enrolled 635 patients. The transition study with 283 patients was
designed to evaluate the two dosing regimens among patients who had
achieved viral levels below the level of detection (<400 copies/mL)
after six months on triple therapy with approved dosing (800 mg every
eight hours) of Crixivan.

Analysis -- Initial Therapy Study

Efficacy results from the preliminary intent-to-treat analysis of the
initial therapy study were based on a total of 287 patients. At week
16, 78 percent of patients on the approved dosing regimen compared to 72
percent on the twice-daily regimen had viral load levels below 400
copies/mL. Among the 87 patients who had been followed in the study
through 24 weeks, 91 percent of the group on the approved dosing regimen
had viral load levels below 400 copies/mL, compared to 64 percent of the
patients on the twice-daily arm.

Patients enrolling in the study had CD4 counts greater than 100
cells/mm3 and viral RNA levels greater than 10,000 copies/mL. The study
started in November 1997 and was being conducted at 49 sites around the
world.

Discontinuation rates were low and similar for both groups in the
initial treatment study, although there was a trend toward more
discontinuations due to nausea and vomiting in the twice-daily group
compared to the approved- dosing group.

Important Cautionary Information About Crixivan

There are some common and AIDS-related medications that should not be
taken with Crixivan. Crixivan should not be administered concurrently
with terfenadine, cisapride, astemiozole, triazolam, midazolam or ergot
derivatives.

Crixivan can be taken with a light meal or on an empty stomach.
Crixivan is generally well-tolerated. There are side effects associated
with protease inhibitors in general and Crixivan in particular. Some
patients treated with Crixivan may develop kidney stones. For some,
this can lead to more severe kidney problems including kidney failure.
Drinking at least six glasses of water (1.5 L) each day may help reduce
the chance of forming a kidney stone.

Other side effects reported include rapid breakdown of red blood cells
and liver problems. As with other protease inhibitors, increased
bleeding in some patients with hemophilia and increased blood sugar
levels or diabetes have been reported.

About Crixivan

More than 170,000 people with HIV/AIDS around the world are on treatment
with Crixivan today, and it is now approved in more than 80 countries.
Crixivan is the most widely prescribed protease inhibitor in the world.

Merck & Co., Inc., is a global research-driven pharmaceutical company
that discovers, develops, manufactures and markets a broad range of
human and animal health products, directly and through its joint
ventures, and provides pharmaceutical benefit services through
Merck-Medco Managed Care.

The patient prescribing information for Crixivan is attached. Full
prescribing information is available by calling 1-800-753-0352, ext.
706.

Crixivan(R) is the Merck registered trademark for indinavir sulfate.

(a) Zidovudine (Retrovir(R) or AZT), Glaxo Wellcome

(b) Lamivudine (Epivir(R) or 3TC), Glaxo Wellcome

CRIXIVAN(R)* (indinavir sulfate) Capsules

Patient Information about

CRIXIVAN (KRIK-sih-van)

for HIV (Human Immunodeficiency Virus) Infection

Generic name: indinavir (in-DIH-nuh-veer) sulfate

Please read this information before you start taking CRIXIVAN. Also,
read the leaflet each time you renew your prescription, just in case
anything has changed. Remember, this leaflet does not take the place of
careful discussions with your doctor. You and your doctor should
discuss CRIXIVAN when you start taking your medication and at regular
checkups. You should remain under a doctor's care when using CRIXIVAN
and should not change or stop treatment without first talking with your
doctor.

What is CRIXIVAN?

CRIXIVAN is an oral capsule used for the treatment of HIV (Human
Immunodeficiency Virus). HIV is the virus that causes AIDS (acquired
immune deficiency syndrome). CRIXIVAN is a type of HIV drug called a
protease (PRO-tee-ase) inhibitor.

How does CRIXIVAN work?

CRIXIVAN is a protease inhibitor that fights HIV. CRIXIVAN can help
reduce your chances of getting illnesses associated with HIV. CRIXIVAN
can also help lower the amount of HIV in your body (called "viral load")
and raise your CD4 (T) cell count. CRIXIVAN may not have these effects
in all patients.

CRIXIVAN is usually prescribed with other anti-HIV drugs such as ZDV
(also called AZT), 3TC, ddI, ddC, or d4T. CRIXIVAN works differently
from these other anti-HIV drugs. Talk with your doctor about how you
should take CRIXIVAN.

CRIXIVAN has been studied in adults. The safety and effectiveness of
CRIXIVAN in children and adolescents have not been established.

How should I take CRIXIVAN?

There are six important things you must do to help you benefit from
CRIXIVAN:

Take CRIXIVAN capsules every day as prescribed by your doctor.
Continue taking CRIXIVAN unless your doctor tells you to stop. Take
the exact amount of CRIXIVAN that your doctor tells you to take, right
from the very start. To help make sure you will benefit from
CRIXIVAN, you must not skip doses or take "drug holidays." If you
don't take CRIXIVAN as prescribed, the activity of CRIXIVAN may be
reduced (due to resistance).

Take CRIXIVAN capsules every 8 hours around the clock, every day.

It may be easier to remember to take CRIXIVAN if you take it at the same
time every day. If you have questions about when to take CRIXIVAN,
your doctor or health care provider can help you decide what schedule
works for you.

If you miss a dose by more than 2 hours, wait and then take the next
dose at the regularly scheduled time. However, if you miss a dose by
less than 2 hours, take your missed dose immediately. Then take your
next dose at the regularly scheduled time. Do not take more or less
than your prescribed dose of CRIXIVAN at any one time.

Take CRIXIVAN with water. You can also take CRIXIVAN with other
beverages such as skim or non-fat milk, juice, coffee, or tea.

Ideally, take each dose of CRIXIVAN without food but with water at
least one hour before or two hours after a meal. Or you can take
CRIXIVAN with a light meal.

Examples of light meals include:

Dry toast with jelly, juice, and coffee (with skim or non-fat milk
and sugar if you want) cornflakes with skim or non-fat milk and sugar

Do not take CRIXIVAN at the same time as any meals that are high in
calories, fat, and protein (for example -- a bacon and egg breakfast).
When taken at the same time as CRIXIVAN, these foods can interfere
with CRIXIVAN being absorbed into your bloodstream and may lessen its
effect.

6. It is critical that you drink at least six 8-ounce glasses of
liquids (preferably water) throughout the day, every day. CRIXIVAN can cause
kidney stones. Having enough fluids in your body should help reduce
the chances of forming a kidney stone. Call your doctor or other
health care provider if you develop kidney pains (middle to lower
stomach or back pain) or blood in the urine.

Does CRIXIVAN cure HIV or AIDS?

CRIXIVAN is not a cure for HIV or AIDS. People taking CRIXIVAN may
still develop infections or other conditions associated with HIV.
Because of this, it is very important for you to remain under the care
of a doctor. Although CRIXIVAN is not a cure for HIV or AIDS, CRIXIVAN
can help reduce your chances of getting illnesses, including death,
associated with HIV. CRIXIVAN may not have these effects in all
patients.

Does CRIXIVAN reduce the risk of passing HIV to others?

CRIXIVAN has not been shown to reduce the risk of passing HIV to others
through sexual contact or blood contamination.

Who should not take CRIXIVAN?

Do not take CRIXIVAN if you have had a serious allergic reaction to
CRIXIVAN or any of its components.

What other medical problems or conditions should I discuss with my
doctor?

Talk to your doctor if:

You are pregnant or if you become pregnant while you are taking
CRIXIVAN.

We do not yet know how CRIXIVAN affects pregnant women or their
developing babies.

You are breast-feeding. You should stop breast-feeding if you are
taking CRIXIVAN.

Also talk to your doctor if you have:

Problems with your liver, especially if you have mild or moderate
liver disease caused by cirrhosis.

Problems with your kidneys.

Diabetes

Hemophilia

Tell your doctor about any medicines you are taking or plan to take,
including non-prescription medicines.

Can CRIXIVAN be taken with other medications?

Drugs you should not take with CRIXIVAN: **

SELDANE(R)
(terfenadine)

HISMANAL(R)
(astemizole)

VERSED(R)
(midazolam)

HALCION(R)
(triazolam)

PROPULSID(R)
(cisapride)

Ergot medications
(e.g., Wigraine(R) and Cafergot(R)

Taking CRIXIVAN with the above medications could result in serious or
life-threatening problems (such as irregular heartbeat or excessive
sleepiness).

In addition, you should not take CRIXIVAN with rifampin, known as
RIFADIN(R), RIFAMATE(R), RIFATER(R), or RIMACTANE(R).

VIDEX(R) (didanosine, ddI) -- If you take CRIXIVAN with VIDEX(R), take
them at least one hour apart.

MYCOBUTIN(R) (rifabutin) -- If you take CRIXIVAN with MYCOBUTIN(R),
your doctor may adjust both the dose of MYCOBUTIN and the dose of CRIXIVAN.

NIZORAL(R) (ketoconazole) -- If you take CRIXIVAN with NIZORAL(R), your
doctor may adjust the dose of CRIXIVAN.

Talk to your doctor about any medications you are taking.

What are the possible side effects of CRIXIVAN?

Like all prescription drugs, CRIXIVAN can cause side effects. The
following is not a complete list of side effects reported with CRIXIVAN
when taken either alone or with other anti-HIV drugs. Do not rely on
this leaflet alone for information about side effects. Your doctor can
discuss with you a more complete list of side effects.

Some patients treated with CRIXIVAN developed kidney stones. In some of
these patients this led to more severe kidney problems, including kidney
failure or inflammation of the kidneys. Drinking at least six 8-ounce
glasses of liquid (preferably water) each day should help reduce the
chances of forming a kidney stone. Call your doctor or other health
care provider if you develop kidney pains (middle to lower stomach or
back pain) or blood in the urine.

Some patients treated with CRIXIVAN have had rapid breakdown of red
blood cells (hemolytic anemia) which in some cases was severe or
resulted in death.

Some patients treated with CRIXIVAN have had liver problems including
liver failure and death. Some patients had other illnesses or were
taking other drugs. It is uncertain if CRIXIVAN caused these liver
problems.

Diabetes and high blood sugar (hyperglycemia) have occurred in patients
taking protease inhibitors. In some of these patients, this led to
ketoacidosis, a serious condition caused by poorly controlled blood
sugar. Some patients had diabetes before starting protease inhibitors,
others did not. Some patients required adjustments to their diabetes
medication. Others needed new diabetes medication.

In some patients with hemophilia, increased bleeding has been reported.

Clinical Studies

Increases in bilirubin (one laboratory test of liver function) have been
reported in approximately 10% of patients. Usually, this finding has
not been associated with liver problems. However, on rare occasions, a
person may develop yellowing of the skin and/or eyes.

Other side effects reported since CRIXIVAN has been marketed include:
abdominal swelling; inflammation of the kidneys; increased fat appearing
in areas such as the neck, abdomen, and back; change in skin color;
severe skin reactions; hair loss; crystals in the urine; and allergic
reactions.

Tell your doctor promptly about these or any other unusual symptoms. If
the condition persists or worsens, seek medical attention.

How should I store CRIXIVAN capsules?

Keep CRIXIVAN capsules in the bottle they came in and at room
temperature (59 degrees - 86 degrees F).

Keep CRIXIVAN capsules dry by leaving the small desiccant "pillow"in
the bottle. Keep the bottle closed.

This medication was prescribed for your particular condition. Do not
use it for any other condition or give it to anybody else. Keep
CRIXIVAN and all medicines out of the reach of children. If you suspect
that more than the prescribed dose of this medicine has been taken,
contact your local poison control center or emergency room immediately.

This leaflet provides a summary of information about CRIXIVAN. If you
have any questions or concerns about either CRIXIVAN or HIV, talk to
your doctor.
** The brands listed are the registered trademarks of their respective
owners and are not trademarks of Merck & Co., Inc.